Palladium-catalyzed direct CH bond arylation of simple arenes with aryltrimethylsilanes

Article abstract of DOI:10.1246/cl.2011.1050

Direct CH bond arylation of arenes with aryltrimethylsilanes catalyzed by PdCl₂ in the presence of CuCl₂ as an oxidant has been developed. In addition to the role as the oxidant, CuCl₂ is found to be necessary for the selective crosscoupling reaction.

Full text of DOI:10.1246/cl.2011.1050

doi:10.1246/cl.2011.1050
1050
Published on the web September 5, 2011
Palladium-catalyzed Direct C-H Bond Arylation of Simple Arenes
with Aryltrimethylsilanes
Kenji Funaki,1 Hiroshi Kawai,1 Tetsuo Sato,1,2 and Shuichi Oi*1,2
1Department of Applied Chemistry, Graduate School of Engineering, Tohoku University,
6-6-11 Aramaki-Aoba, Aoba-ku, Sendai, Miyagi 980-8579
2Environment Conservation Research Institute, Tohoku University,
6-6-11 Aramaki-Aoba, Aoba-ku, Sendai, Miyagi 980-8579
(Received July 4, 2011; CL-110568; E-mail: oishu@aporg.che.tohoku.ac.jp)
Direct C-H bond arylation of arenes with aryltrimethyl-
Table 1. Direct C-H bond arylation of naphthalene with
phenylsilicon reagentsa
silanes catalyzed by PdCl2 in the presence of CuCl2 as an
oxidant has been developed. In addition to the role as the
oxidant, CuCl2 is found to be necessary for the selective cross-
coupling reaction.
PdCl2 5 mol%
oxidant 2.0 mmol
PhSiR3
+
1,2-DCE 0.5 mL
80 °C, 16 h
Ph
Ph
Ph
Ph-Ph
+
+
Biaryl structures are very important units in fine chemicals,
such as organic electronic materials, pharmaceuticals, and
agrochemicals. The cross-coupling reactions of various aryl-
metal reagents with aryl halides catalyzed by nickel or palladium
have been widely utilized for the biaryl synthesis.1,2 In recent
years, transition-metal-catalyzed direct C-H bond arylation has
attracted significant attention as an efficient and useful method
for biaryl synthesis.3 There have been many studies of direct
arylation of highly electron-rich heteroaromatic compounds4 and
arenes involving nitrogen- or oxygen-based directing groups.5
In contrast, the direct arylation of simple aromatic hydrocarbons,
such as naphthalene and phenanthrene, has been less studied.6
In the previous work, we reported the direct C-H bond
arylation of simple arenes with aryltin trichlorides in the
presence of a catalytic amount of Pd(II) salt and stoichiometric
amount of CuCl2.6b The reaction mechanism is proposed to
involve a highly electrophilic arylpalladium intermediate which
would easily react with arenes via electrophilic substitution.
Since aryltin trichlorides are difficult to handle and highly toxic,
we set out to develop more practical direct C-H bond arylation
using arylsilicon compounds, which are easy to handle, show
low toxicity, and are easily available, as alternative arylmetal
reagents. Herein, we report that aryltrimethylsilanes successfully
reacted with simple arenes to give the corresponding cross-
coupling products in the presence of palladium catalyst and
CuCl2 as the oxidant and activator of the catalyst. To the best of
our knowledge, there has been no example of the direct C-H
bond arylation using aryltrialkylsilanes.7
At first, the reactions of naphthalene (0.5 mmol) with
phenylsilicon reagents (1.0 mmol) were examined using PdCl2
(5 mol %, 0.025 mmol) and oxidants (2.0 mmol) in 1,2-dichloro-
ethane (1,2-DCE, 0.5 mL) at 80 °C for 16 h (Table 1). After the
screening, desired products 2a and 3a were obtained in moderate
yields by the use of PhSiMe3 (1a) and CuCl2 (Entry 1). When
the amount of 1a was increased to 2.0 mmol, the total yield of
the cross-coupling products was increased to 59% (Entry 2). In
the case of phenylsilanes with bulky alkyl groups on the silicon,
the yields of the coupling products were decreased considerably
(Entries 3 and 4). The use of phenylalkoxysilanes, which are
known to be good reagents for coupling reactions,8 decreased
the yields of 2a and 3a (Entries 5-7). The reaction of PhSiCl3
2a
3a
4
Yield/%b
2ac (¡:¢) 3ac 4d
38 (87:13)
35 (89:11) 24 12
Entry PhSiR3
Oxidant
1
PhSiMe3 (1a)
CuCl2
CuCl2
CuCl2
CuCl2
7
0
2e 1a
3
4
PhSiEt3
PhSii-Pr3
30 (83:17)
0
23 (83:17)
16 (81:19)
4
0
2
6
4
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
3
0
31
1
0
0
1
0
0
1
5
6
PhSiMe2(OEt) CuCl2
PhSiMe(OMe)2 CuCl2
7
PhSi(OMe)3
CuCl2
CuCl2
Cu(OAc)2
CuSO4
CuF2
(100:0)
8
9
PhSiCl3
1a
(79:21)
(94:6)
(88:12)
10
11
12
13
1a
1a
1a
1a
CuBr2
none
CuCl2
0
0
14f 1a
aReaction conditions: Naphthalene (0.5 mmol), phenylsilicon
reagent (1.0 mmol), PdCl2 (0.025 mmol), and oxidant (2.0
mmol) in 1,2-DCE (0.5 mL) at 80 °C for 16 h. bDetermined by
GC. Based on naphthalene. Based on phenylsilicon reagent.
e2.0 mmol of PhSiMe3 was used. Reaction without PdCl2.
c
d
f
did not proceed in the present catalytic system (Entry 8). Among
the several oxidants examined, CuCl2 showed the best result
(Entries 9-12). In addition, the reaction without the oxidant
did not proceed at all (Entry 13). The use of other palladium
catalysts, such as Pd(OAc)2, [PdCl2(MeCN)2], [PdCl2(PhCN)2],
[PdCl2(cod)], and [Pd2(dba)3], decreased the yield of the cross-
coupling product (4-26% yield) and increased the yield of bi-
phenyl (4) (30-81% yield). Palladium complexes with electron-
donating ligands, such as [PdCl2(PPh3)2] and [PdCl2(bpy)], did
not give any coupling products. As a control experiment, the
reaction without palladium catalyst did not proceed (Entry 14).
The predominant formation of the ¡-coupling product strongly
suggests that the reaction pathway involves an electrophilic
substitution on the naphthalene ring.
Chem. Lett. 2011, 40, 1050-1052
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www.csj.jp/journals/chem-lett/

1051
Table 2. Investigation of the effect of CuCl2
10
Ph
Ph
9
PdCl2 0.1 mmol
CuCl2 x mmol
and
and
1a
+
+
Ph-Ph
2
5
4
Ph
1,2-DCE 1.0 mL
3
Ph
Ph
3
4
Ph
Ph
80°C, 3 h
2a
4
0.5 mmol
1.0 mmol
48%, 2b
(C2:C3=8:92)
46%, 3b
(C4:C5=80:20)
34%, 2c
14%, 3c
(C9:C10=45:55)
mmol by GC
2a
Entry
CuCl2, x/mmol
2a:4
4
1
0
0
1.0
1.0
2.0
3.0
0
0
0
®
0:1
1.1:1
1:27
10:1
25:1
Me
2a
3
0.071
0.040
0.40
0.005
0.003
Ph
69%, 2d
0.044
0.015
0.049
0.074
4a
5
6
67%, 2e
15%, 2f
Me
a[PdCl2(MeCN)2] (0.1 mmol) was used instead of PdCl2.
45%, 2h
47%, 2g
OMe
CF3
Ph
PdCl2 5 mol%
CuCl2 2.0 mmol
1a 1.0 mmol
13%, 2a
0.25 mmol
+
81%, 2i
77%, 2j
72%, 2k
F
Cl
Br
+
Ph
1,2-DCE 0.5 mL
80 °C, 3 h
Scheme 1. Direct C-H bond arylation of several arenes with
aryltrimethylsilanes.
D8
D7
11%, 2a-D7
kH/kD = 1.16
0.25 mmol
Scheme 1 shows the results of the direct arylation of several
arenes with various aryltrimethylsilanes under the optimized
reaction conditions (Table 1, Entry 2). The reaction of fluoran-
thene with 1a afforded mono- and diphenylated products in 48%
(2b, C2:C3 = 8:92) and 46% yield (3b, C4:C5 = 80:20),
respectively. Phenylation of pyrene gave 4-phenylpyrene (2c)
in 34% yield and diphenylated pyrene 3c in 14% yield
(C9:C10 = 45:55). The reactions of phenanthrene with various
aryltrimethylsilanes having both electron-donating and -with-
drawing groups at their 4-positions gave the corresponding
9-arylphenanthrenes 2d, 2e, and 2g–2k in 45 to 81% yields. A
clear correlation between the electronic properties of the
aryltrimethylsilanes and the product yields was not observed.
It is noted that 4-halogenated phenyltrimethylsilanes gave
halogen-substituted products 2i-2k, which can be used for
further coupling reactions at the halogen substituents. The
reaction using sterically hindered o-tolyltrimethylsilane gave the
product 2f in a low yield of 15%.13
To clarify the role of CuCl2, effect of the amount of CuCl2
was then examined in the reaction of naphthalene (0.5 mmol)
with 1a (1.0 mmol) using PdCl2 (0.10 mmol) in 1,2-DCE
(1.0 mL) at 80 °C (Table 2). The reactions were carried out for
3 h to form only monophenylated product 2a. The reaction
without CuCl2 did not give any coupling products, because of
insolubility of PdCl2 (Entry 1). Thus, the use of soluble
[PdCl2(MeCN)2] without CuCl2 gave only biphenyl (4) as the
homocoupling product of 1a (Entry 2). The reaction using PdCl2
with 1.0 mmol of CuCl2 afforded the cross-coupling product 2a
together with almost the same amount of 4 (Entry 3). On the
other hand, the use of [PdCl2(MeCN)2] with 1.0 mmol of CuCl2
gave 4 predominantly (Entry 4). Addition of larger amounts of
CuCl2 to PdCl2 catalyst then resulted in the preferential
formation of 2a (Entries 5 and 6). These results show that the
amount of CuCl2 affects the reaction selectivity between cross-
coupling and homocoupling reactions. It is reasonable to
Scheme 2. Kinetic isotope effect on the reaction of naphtha-
lene with 1a.
PdCl2
CuCl2
(i)
ArSiMe3
Ar-PdCl (CuCl )
PdCl2 (CuCl )
•
•
2 n
2 n
- ClSiMe3
2CuCl2
- 2CuCl
Ar'H
- HCl
(iv)
(ii)
cross
Ar-Ar' + Pd (CuCl )
(iii)
Ar-Pd (CuCl )
•
•
2 n
2 n
Ar'
Scheme 3. A presumed reaction pathway.
suppose that this reaction selectivity is caused by the formation
of polymetallic Pd-Cu clusters.9,10 It is also possible that CuCl2
oxidizes a Pd(II) intermediate to a Pd(III) or Pd(IV) species.11
Acetonitrile ligands on the palladium catalyst would prevent
such interactions between palladium and copper.
Kinetic isotope effect was also investigated by the com-
petitive reaction between naphthalene and naphthalene-D8 with
1a (Scheme 2). The kH/kD ratio was determined to be 1.16. This
suggests that the C-H bond cleavage of naphthalene by a
palladium intermediate proceeds via the electrophilic substitu-
tion mechanism.
A presumed reaction pathway is shown in Scheme 3.
Electrophilic transmetalation of PdCl2 with ArSiMe3 at the
ipso-Si position12 generates an arylpalladium intermediate in the
presence of CuCl2 (i). Aromatic electrophilic substitution of
Ar¤-H with the arylpalladium intermediate occurs to form a
diarylpalladium intermediate (ii). The exact structure of the
arylpalladium intermediate has not yet been clear, the interaction
with CuCl2 would be crucial in this step. Reductive elimination
Chem. Lett. 2011, 40, 1050-1052
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1052
from the diarylpalladium species gives the cross-coupling
products (iii). Finally, oxidation of palladium species by CuCl2
regenerates PdCl2 (iv).
In summary, palladium-catalyzed direct C-H bond arylation
of simple arenes with aryltrimethylsilanes is described. In this
reaction, CuCl2 is essential to obtain the desired cross-coupling
products in high selectivity. Further studies to expand the
substrate scope and their applications, as well as the inves-
tigations for the reaction mechanism are now in progress.
8946. e) J. Huang, J. Chan, Y. Chen, C. J. Borths, K. D.
Baucom, R. D. Larsen, M. M. Faul, J. Am. Chem. Soc. 2010,
132, 3674. f) F. Shibahara, E. Yamaguchi, T. Murai, J. Org.
Chem. 2011, 76, 2680.
5
a) Z. Shi, B. Li, X. Wan, J. Cheng, Z. Fang, B. Cao, C. Qin,
Y. Wang, Angew. Chem., Int. Ed. 2007, 46, 5554. b) D.-H.
Wang, T.-S. Mei, J.-Q. Yu, J. Am. Chem. Soc. 2008, 130,
17676. c) J.-H. Chu, S.-L. Tsai, M.-J. Wu, Synthesis 2009,
3757. d) V. S. Thirunavukkarasu, K. Parthasarathy, C.-H.
Cheng, Chem.®Eur. J. 2010, 16, 1436. e) G.-W. Wang, T.-T.
Yuan, D.-D. Li, Angew. Chem., Int. Ed. 2011, 50, 1380.
a) G. Dyker, S. Borowski, J. Heiermann, J. Körning, K.
Opwis, G. Henkel, M. Köckerling, J. Organomet. Chem.
2000, 606, 108. b) H. Kawai, Y. Kobayashi, S. Oi, Y. Inoue,
Chem. Commun. 2008, 1464. c) C. Qin, W. Lu, J. Org.
Chem. 2008, 73, 7424.
a) S. Yang, B. Li, X. Wan, Z. Shi, J. Am. Chem. Soc. 2007,
129, 6066. b) H. Zhou, Y.-H. Xu, W.-J. Chung, T.-P. Loh,
Angew. Chem., Int. Ed. 2009, 48, 5355. c) H. Hachiya, K.
Hirano, T. Satoh, M. Miura, Angew. Chem., Int. Ed. 2010,
49, 2202. d) Z. Liang, B. Yao, Y. Zhang, Org. Lett. 2010, 12,
3185.
a) M. E. Mowery, P. DeShong, Org. Lett. 1999, 1, 2137. b)
H. M. Lee, S. P. Nolan, Org. Lett. 2000, 2, 2053. c) C. Wolf,
R. Lerebours, Org. Lett. 2004, 6, 1147. d) L. Zhang, J. Qing,
P. Yang, J. Wu, Org. Lett. 2008, 10, 4971.
a) D. R. Stuart, E. Villemure, K. Fagnou, J. Am. Chem. Soc.
2007, 129, 12072. b) S. Potavathri, A. S. Dumas, T. A.
Dwight, G. R. Naumiec, J. M. Hammann, B. DeBoef,
Tetrahedron Lett. 2008, 49, 4050.
This work was supported in part by a Grant-in-Aid for
Scientific Research on Innovative Areas “Molecular Activation
Directed toward Straightforward Synthesis” from MEXT, Japan
and by a commissioned project conducted by New Energy and
Industrial Technology Development Organization (NEDO).
6
7
This paper is in celebration of the 2010 Nobel Prize
awarded to Professors Richard F. Heck, Akira Suzuki, and
Ei-ichi Negishi.
References and Notes
1
a) Cross-Coupling Reactions: A Practical Guide in Topics in
Current Chemistry, ed. by N. Miyaura, Springer-Verlag,
Berlin, 2002, Vol. 219. doi:10.1007/3-540-45313-X. b)
Metal-Catalyzed Cross-Coupling Reactions, 2nd ed., ed.
by A. de Meijere, F. Diederich, Wiley-VCH, Weinheim,
2004.
8
9
2
3
Reviews: a) M. Kumada, Pure Appl. Chem. 1980, 52, 669. b)
E. Negishi, Acc. Chem. Res. 1982, 15, 340. c) N. Miyaura,
A. Suzuki, Chem. Rev. 1995, 95, 2457. d) T. Hiyama, Y.
Hatanaka, Pure Appl. Chem. 1994, 66, 1471. e) J. K. Stille,
Angew. Chem., Int. Ed. Engl. 1986, 25, 508.
Reviews: a) T. Satoh, M. Miura, Chem. Lett. 2007, 36, 200.
b) I. V. Seregin, V. Gevorgyan, Chem. Soc. Rev. 2007, 36,
1173. c) D. Alberico, M. E. Scott, M. Lautens, Chem. Rev.
2007, 107, 174. d) F. Kakiuchi, T. Kochi, Synthesis 2008,
3013. e) O. Daugulis, H.-Q. Do, D. Shabashov, Acc. Chem.
Res. 2009, 42, 1074. f) X. Chen, K. M. Engle, D.-H. Wang,
J.-Q. Yu, Angew. Chem., Int. Ed. 2009, 48, 5094. g) L.
Ackermann, R. Vicente, A. R. Kapdi, Angew. Chem., Int. Ed.
2009, 48, 9792. h) T. W. Lyons, M. S. Sanford, Chem. Rev.
2010, 110, 1147. i) C.-L. Sun, B.-J. Li, Z.-J. Shi, Chem.
Commun. 2010, 46, 677. j) C. Liu, H. Zhang, W. Shi, A. Lei,
Chem. Rev. 2011, 111, 1780.
10 a) T. Hosokawa, M. Takano, S.-I. Murahashi, J. Am. Chem.
Soc. 1996, 118, 3990. b) T. Hosokawa, T. Nomura, S.-I.
Murahashi, J. Organomet. Chem. 1998, 551, 387.
11 a) B. D. Dangel, J. A. Johnson, D. Sames, J. Am. Chem. Soc.
2001, 123, 8149. b) D. Kalyani, A. R. Dick, W. Q. Anani,
M. S. Sanford, Org. Lett. 2006, 8, 2523. c) X. Wan, Z. Ma,
B. Li, K. Zhang, S. Cao, S. Zhang, Z. Shi, J. Am. Chem. Soc.
2006, 128, 7416. d) M. Wasa, J.-Q. Yu, J. Am. Chem. Soc.
2008, 130, 14058. e) R. B. Bedford, J. U. Engelhart, M. F.
Haddow, C. J. Mitchell, R. L. Webster, Dalton Trans. 2010,
39, 10464.
12 a) C. Eaborn, J. Organomet. Chem. 1975, 100, 43. b) J.-M.
Valk, J. Boersma, G. van Koten, J. Organomet. Chem. 1994,
483, 213. c) P. Steenwinkel, R. A. Gossage, T. Maunula,
D. M. Grove, G. van Koten, Chem.®Eur. J. 1998, 4, 763. d)
W. Rauf, J. M. Brown, Synlett 2009, 3103. e) W. Rauf, A. L.
Thompson, J. M. Brown, Chem. Commun. 2009, 3874.
13 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
4
a) S.-D. Yang, C.-L. Sun, Z. Fang, B.-J. Li, Y.-Z. Li, Z.-J.
Shi, Angew. Chem., Int. Ed. 2008, 47, 1473. b) L.
Ackermann, R. Vicente, Org. Lett. 2009, 11, 4922. c) B.
Liégault, D. Lapointe, L. Caron, A. Vlassova, K. Fagnou,
J. Org. Chem. 2009, 74, 1826. d) K. Ueda, S. Yanagisawa,
J. Yamaguchi, K. Itami, Angew. Chem., Int. Ed. 2010, 49,
Chem. Lett. 2011, 40, 1050-1052
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/